Tetrabutylammonium Fluoride → 7-Ethynylisoindolin-1-one

To a solution of 7-((trimethylsilyl)ethynyl)isoindolin-1-one (160) (0.172 g, 0.634 mmol) in dry THF (8 mL) under an atmosphere of nitrogen was added TBAF (1.0 M in THF, 0.697 mL, 0.697 mmol) dropwise at 0° C. The solution was stirred at this temperature for 1.5 hours and then quenched by the addition of water (2 mL). The reaction mixture was concentrated in vacuo and diluted with DCM (100 mL) and sat. aq. NaHCO3 (70 mL). The layers were separated and the aqueous layer was extracted with DCM (70 mL), the combined organic layers were washed with water (100 mL), brine (100 mL), dried (MgSO4), filtered and concentrated in vacuo to give a beige solid. The crude product was purified by silica gel chromatography (Biotage Isolera, 12 g Si Cartridge, 0-80% EtOAc in DCM) to give the title compound (I61) (0.076 g, 76% yield) as an off-white solid; 1H NMR (400 MHz, d6-DMSO) δ 8.59 (s, 1H), 7.61-7.50 (m, 3H), 4.39 (s, 1H), 4.33 (s, 2H). LCMS Method C: rt 4.56 min, m/z 158.1 [M+H]+

1. customquenched by the addition of water (2 mL)
2. concentrationThe reaction mixture was concentrated in vacuo
3. additiondiluted with DCM (100 mL) and sat. aq. NaHCO3 (70 mL)
4. customThe layers were separated
5. extractionthe aqueous layer was extracted with DCM (70 mL)
6. washthe combined organic layers were washed with water (100 mL), brine (100 mL)
7. dry with materialdried (MgSO4)
8. filtrationfiltered
9. concentrationconcentrated in vacuo
10. customto give a beige solid
11. customThe crude product was purified by silica gel chromatography (Biotage Isolera, 12 g Si Cartridge, 0-80% EtOAc in DCM)

ORD record

ord-4e8ebf08faa0431a85a40b945643b09d

Source dataset

uspto-grants-2016_08

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09421205B2